Pre Clinical Discovery Core

总结 临床前研究对于靶点的识别和验证、机理的检测和治疗是必要的。 假设，并在适当的临床前动物模型中进行初步概念验证研究，并代表 这是将功能促进疗法（FPT）推进到人体试验的必要前提。一个重要方面 在模式生物的转化研究是基本的主张，生理过程， 在动物模型中进行评价时，与在人体中观察到的情况足够相似， 效果外推此外，为了对临床前研究的结果进行有意义的解释， 测量必须是可再现的、准确的，并且与在人类中观察到的条件足够相似。 因此，波士顿OAIC建立了临床前发现核心，提供标准化的 用于分析肌肉性能和身体功能的程序和最先进的设备， 肌肉生物能量学、非侵入性成像和全身代谢结果。PDC提供 标准化的、最先进的方法和仪器来评估身体成分（瘦体重、整体 身体和局部脂肪量，骨骼肌质量，使用高分辨率的肌肉功能显微镜 磁共振成像），以量化响应于 功能促进疗法。PDC还为早期职业调查人员提供咨询服务， 优化研究设计，指导选择合适的实验模型和结局指标。 PDC已经制定了培训和认证相关工作人员的标准化程序， 在其程序中保持严格的质量控制。标准作业程序已获得批准， 参与机构的动物中心，以便从参与机构 实验室到PDC设施。PDC继续创新并提供新的测量模式， 促进FPT发现。PDC领导层与设备制造商密切合作， 改进方法，提高时间分辨率（信噪比）、精度和灵敏度， 它提供的技术。拟议的发展项目将采用超高场7特斯拉磁 用于骨骼肌中NAD+/NADH的非侵入性测量的共振光谱（MRS）方法 肌肉和脑，使得能够在没有组织活检的情况下体内评估线粒体效率。 PDC已成为OAIC资助的REC和PESC项目以及外部资助项目的独特资源。 使用临床前模型进行FPT发现研究的OAIC项目。PDC支持的研究包括 协助OAIC研究人员成功提交了几份NIH资助申请和同行评审的出版物。

Summary The preclinical studies are necessary for target identification and validation, for testing mechanistic hypotheses, and for initial proof-of-concept studies in appropriate pre-clinical animal models and represent an essential pre-requisite for advancing function promoting therapies (FPTs) to human trials. An important aspect of translational research in model organisms is the underlying assertion that the physiological processes that are evaluated in animal models are sufficiently similar to conditions observed in humans to allow dose and effect extrapolation. Additionally, for the outcomes of preclinical studies to be meaningfully interpreted, measurements must be reproducible, accurate, and sufficiently similar to the conditions observed in humans. Accordingly, the Boston OAIC has established a Preclinical Discovery Core that offers standardized procedures and state-of-the-art equipment for the analysis of muscle performance and physical function, muscle bioenergetics, and non-invasive imaging and whole body metabolic outcomes. The PDC provides standardized, state-of-the-art methods and instruments to assess body composition (lean body mass, whole body and regional fat mass, skeletal muscle mass, functional microscopy of the muscle using high resolution magnetic resonance imaging) in animal models of aging and disease to quantify outcomes in response to function promoting therapies. The PDC also offers consultative services to early career investigators to optimize study design, and guide the selection of appropriate experimental model and outcome measures. The PDC has established standardized procedures for training and certification of its staff involved, and for maintaining strict quality control in its procedures. The standard operating procedures have been approved by the IACUCs of the participating institutions to enable streamlined transfer of animals from the participating laboratory to the PDC facility. The PDC continues to innovate and provide novel measurement modalities to facilitate FPT discovery. The PDC leadership has worked closely with equipment manufacturers to continually refine the methods and improve the temporal resolution (signal to noise ratio), precision, and sensitivity of the techniques that it offers. The proposed developmental project will apply an ultra-high-field 7-tesla Magnetic Resonance Spectroscopy (MRS) method for the non-invasive measurement of NAD+/NADH in the skeletal muscle and brain enabling an in vivo assessment of mitochondrial efficiency without a tissue biopsy. The PDC has become a unique resource for OAIC-funded REC and PESC projects, and for externally-funded OAIC projects that are using preclinical models for FPT discovery research. The PDC supported studies have facilitated several successful NIH grant submissions and peer reviewed publications by OAIC investigators.